This application responds to Program Announcement Number PAR-07-214 (Academic-Industrial Partnerships for Development and Validation of In Vivo Imaging Systems and Methods for Cancer Investigations) by proposing a 3-way partnership between Dartmouth, University of Massachusetts (UMass) Medical School and Hologic, Inc (Bedford, MA) to develop and validate a new fusion technology for breast imaging - Near Infrared (NIR) spectral tomography (NIRST) integrated with breast tomosynthesis (BTS). The goal is to create a single exam platform that will synergistically combine the functional parameters obtained through NIRST with the high resolution 3D structural information available from BTS to enable diagnostic decisions that exhibit superior ROC characteristics and substantially improved PPVs over current call-back and diagnostic practices associated with breast cancer surveillance. The project capitalizes on the significant technical, clinical and commercial strengths of its three partners. Specifically, Dartmouth provides more than a decade of experience in the development of advanced concepts for application of NIRST in breast imaging including forms that have been successfully fused with other conventional imaging modalities. Dartmouth has also participated as a leading institution in early clinical studies of BTS with the Hologic system. UMass brings accomplishments and expertise in the x-ray physics of breast imaging that includes the development of significant advances in system hardware as well as image processing and reconstruction algorithms which are pivotal to the proposed studies. Hologic, Inc, is the commercial leader in the development of the most advanced BTS technology, has extensive experience in the design and conduct of BTS evaluative clinical trials and is poised to release commercially its second generation system which is expected to gain FDA approval in the near future. The specific aims of the project are: (1) to develop a fusion of NIRST and BTS that progresses to a fully integrated platform where the optical imaging technology is permanently in place during BTS imaging;(2) to develop the x-ray image segmentation and concomitant reconstruction algorithms for defining breast parenchymal patterns as structural priors for NIR image formation;(3) to optimize and characterize the most promising hardware and software outcomes from Aim 1 and Aim 2 and evaluate them in phantoms and early-stage clinical exams to establish feasibility and refine their capabilities in the form of two identical prototypes;(4) to conduct a two- center clinical study designed to demonstrate the validity of the proposed fusion platform and establish the clinical potential of the approach. PUBLIC HEALTH RELEVANCE: Screen-film mammography is an effective method for detecting breast cancer and is the only technique proven to reduce mortality from the disease;however, its limitations are well known and include low sensitivity and positive predictive value, largely caused by the overlap of normal parenchymal tissues in the mammogram, especially in the dense breast. The goal of the proposed project, which represents a three-way academic- industrial partnership, is to create an innovative fusion of Near Infrared (NR) spectral tomography (NIRST) with breast tomosynthesis (BTS) that has been demonstrated to be (i) sufficiently robust with respect to clinical workflow to have been deployed in a two-center clinical study, (ii) validated in terms of its clinical potential to add diagnostic value over BTS alone and (iii) ready for much larger-scale multi-center evaluative clinical trials sufficient for generating the data required for gaining FDA approval.